Biyuan Qiu1, Tao Ma2,3, Chunyan Peng4, Xiaoqin Zheng1, Jiyun Yang2,4,5. 1. 1 Medical Technology College, Chengdu University of Traditional Chinese Medicine of China , Chengdu, Sichuan, P.R. China . 2. 2 Prenatal Diagnosis Center, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital , Chengdu, Sichuan, P.R. China . 3. 3 Department of Gynecology & Obstetrics, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital , Chengdu, Sichuan, P.R. China . 4. 4 School of Medicine, University of Electronic Science and Technology of China , Chengdu, Sichuan, P.R. China . 5. 5 Sichuan Provincial Key Laboratory for Human Disease Gene Study, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital , Chengdu, Sichuan, P.R. China .
Abstract
BACKGROUND: The diagnosis of oculocutaneous albinism (OCA) is established using clinical signs and symptoms. OCA is, however, a highly genetically heterogeneous disease with mutations identified in at least nineteen unique genes, many of which produce overlapping phenotypic traits. Thus, differentiating genetic OCA subtypes for diagnoses and genetic counseling is challenging, based on clinical presentation alone, and would benefit from a comprehensive molecular diagnostic. AIM: To develop and validate a more comprehensive, targeted, next-generation-sequencing-based diagnostic for the identification of OCA-causing variants. MATERIALS AND METHODS: The genomic DNA samples from 28 OCA probands were analyzed by targeted next-generation sequencing (NGS), and the candidate variants were confirmed through Sanger sequencing. RESULTS: We observed mutations in the TYR, OCA2, and SLC45A2 genes in 25/28 (89%) patients with OCA. We identified 38 pathogenic variants among these three genes, including 5 novel variants: c.1970G>T (p.Gly657Val), c.1669A>C (p.Thr557Pro), c.2339-2A>C, and c.1349C>G (p.Thr450Arg) in OCA2; c.459_470delTTTTGCTGCCGA (p.Ala155_Phe158del) in SLC45A2. CONCLUSION: Our findings expand the mutational spectrum of OCA in the Chinese population, and the assay we developed should be broadly useful as a molecular diagnostic, and as an aid for genetic counseling for OCA patients.
BACKGROUND: The diagnosis of oculocutaneous albinism (OCA) is established using clinical signs and symptoms. OCA is, however, a highly genetically heterogeneous disease with mutations identified in at least nineteen unique genes, many of which produce overlapping phenotypic traits. Thus, differentiating genetic OCA subtypes for diagnoses and genetic counseling is challenging, based on clinical presentation alone, and would benefit from a comprehensive molecular diagnostic. AIM: To develop and validate a more comprehensive, targeted, next-generation-sequencing-based diagnostic for the identification of OCA-causing variants. MATERIALS AND METHODS: The genomic DNA samples from 28 OCA probands were analyzed by targeted next-generation sequencing (NGS), and the candidate variants were confirmed through Sanger sequencing. RESULTS: We observed mutations in the TYR, OCA2, and SLC45A2 genes in 25/28 (89%) patients with OCA. We identified 38 pathogenic variants among these three genes, including 5 novel variants: c.1970G>T (p.Gly657Val), c.1669A>C (p.Thr557Pro), c.2339-2A>C, and c.1349C>G (p.Thr450Arg) in OCA2; c.459_470delTTTTGCTGCCGA (p.Ala155_Phe158del) in SLC45A2. CONCLUSION: Our findings expand the mutational spectrum of OCA in the Chinese population, and the assay we developed should be broadly useful as a molecular diagnostic, and as an aid for genetic counseling for OCA patients.